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					Bronchiolitis



Alana Arnold, PharmD
Clinical Coordinator
Children’s Hospital
Objectives
Bronchiolitis

•   Define bronchiolitis
•   Describe etiology and prevalence
•   Define clinical manifestations
•   Describe pathophysiology
•   Describe diagnosis and treatment
•   Identify strategy for prevention
Definition
Bronchiolitis



 Bronchiolitis is an acute inflammation
 of the bronchioles (smaller airways
 that branch off the main airway) and
 is usually caused by a viral infection
 that occurs primarily in young infants,
 most often in those aged 2-24
 months.
Etiology
Bronchiolitis
   The virus is transmitted from person-to-person by direct contact with
    nasal secretions or by airborne droplets.
     – Respiratory syncytial virus: (85% during winter months)
     – Parainfluenza (25%)
     – Adenovirus (5%)

   Other less common etiologic agents include the following:
     – Mycoplasma pneumoniae (5%)
     – Enterovirus (5%)
     – Influenza virus (5%)
     – Rhinovirus (5%)

   RSV generally causes only mild symptoms in adults but can result in severe
    illness in infants often requiring hospitalization.
Prevalence
Bronchiolitis
        In the US:
         Annual incidence:
              11.4% in children younger than 1 year
              6% in those aged 1-2 years
              = 17 % infant hospitalization

         Usually affects children under the age of 2, with a peak age of 3 to 6 months.
          Bronchiolitis occurs as many as 1.5 times more frequently in males.

        Internationally:
         The frequency in developed countries appears to be similar to that in the US.
         Peak incidence usually occurs during winter months in temperate climates and
         during the rainy season in tropical climates.


Shay DK, Holman RC, Newman RD: Bronchiolitis-associated hospitalizations among US children, 1980-1996. JAMA 1999 Oct 20;
282(15): 1440-6[
Risk Factors
Bronchiolitis


   Age (< 6 months old)
   No history of being breastfed
   Prematurity
    – (born before 37 weeks gestation)
   Exposure to cigarette smoke
   Crowded living conditions
Clinical Course
Bronchiolitis

   Bronchiolitis begins as a mild upper respiratory infection that,
    over a period of 2 to 3 days, can develop into a condition of
    increasing respiratory distress with wheezing and a
    "tight" wheezy cough. The infant's breathing rate may
    increase markedly (tachypnea), and the infant may become
    irritable or anxious looking. If the disease is severe
    enough, the infant may turn bluish (cyanotic) which is an
    indication of a critical emergency.

   As the effort of breathing increases, parents may see the
    nostrils flaring with each breath and the muscles between
    the ribs retracting as the child tries to inhale air. This can
    be exhausting for the child, and very young infants may
    simply fatigue to an extent that breathing becomes difficult to
    maintain.
Summary of Clinical Manifestations
Bronchiolitis
  – Cough, wheezing, shortness of breath
  – Rapid breathing (tachypnea)
          often at rates over 50-60 breaths per minute
             – (most common physical sign)
  –   Intercostal retractions
  –   Nasal flaring in infants
  –   Fever (variable) usually in the range of 38.5-39°C
  –   Bluish skin due to lack of oxygen (cyanosis)
  –   Vomiting, especially post-tussive
  –   Irritability
  –   Poor feeding or anorexia
Pathophysiology
Bronchiolitis
   Infection of bronchiolar respiratory and ciliated
    epithelial cells produces increased mucus secretion,
    cell death, and sloughing, followed by a
    peribronchiolar lymphocytic infiltrate and
    submucosal edema.
   Causes Narrowing and obstruction of small airways.
   Resulting in decreased ventilation of portions of the
    lung, resulting in hypoxia. Work of breathing is
    increased due to increased end-expiratory lung
    volume and decreased lung compliance.
Bronchiolitis
Physical and Laboratory Findings
Bronchiolitis

  – Wheezing and crackling sounds are heard by
    stethoscope examination of chest.
  – Decreased blood oxygen levels
  – Tests often include a chest X-ray and blood gases.
  – Antigen tests of nasal washings provide rapid (usually
    within 30 min) and accurate detection of RSV.
          – A positive culture can confirm the diagnosis of RSV infection.
          – Nasal washings should be obtained from children at risk for
            severe disease.
          – Respiratory viral panels, cultures for RSV or other viruses may
            be useful.
  – CBC is seldom useful since the white blood cell (WBC)
    count is usually within normal limits.
Diagnosis
Bronchiolitis

   Other things to consider:
    – Asthma/Apnea
    – Pneumonia
    – Cystic Fibrosis
    – Bronchitis
    – Congestive Heart Failure
Treatment Considerations
Bronchiolitis

     Supportive Care
       – IV fluids
       – Oxygen
     Supportive therapy may also include chest clapping or postural
      drainage to aid in secretion removal.

     Meds
       – Albuterol
       – Epinephrine
       – Ipratropium
       – Steroids
     Antibiotics are NOT effective against viral infections. In extremely ill
      children, antiviral medications (such as ribavirin) are sometimes used.

Taber LH, Knight V, Gilbert BE, et al: Ribavirin aerosol treatment of bronchiolitis associated with respiratory syncytial
      virus infection in infants. Pediatrics 1983 Nov; 72(5): 613-8
Admit ?
Bronchiolitis
   Suggested guidelines for admission
     –   Oxygen saturation less than 94% after therapy.
     –   Respiratory distress (eg, respiratory rate >60/min or retractions at rest)
     –   Apnea
     –   Younger than 2 months or history of prematurity
     –   Underlying cardiopulmonary disease or immunosuppression

   High-risk patients and patients with moderate respiratory distress
    or persistent hypoxemia should be admitted for the following:
     –   Oxygen therapy and apnea monitoring
     –   Restoration and/or maintenance of fluid balance

   Infants with a history of gestational age less than 34 weeks, infants
    younger than 6 weeks, and infants with congenital or acquired
    immunodeficiency are at high risk for severe RSV infection and
    require heightened vigilance.
    Bronchodilators
    (Albuterol)

   Beta-2 agonist relaxes bronchial smooth
    muscle
   The therapeutic use of bronchodilators remains
    controversial because there is conflicting evidence in
    regards to the efficacy of bronchodilators in
    bronchiolitis, it is reasonable to administer albuterol
    (0.15mg/kg/dose) on a trial basis to patients with
    bronchiolitis and access the clinical response. If
    improvement in retractions, respiratory rate and
    wheezing is noted, scheduled aerosol treatments may
    be continued.
Epinephrine

     There is evidence for the use of epinephrine as a
     bronchodilator for patients with bronchiolitis.

      Dosing:
           Injectable:
                SC: 0.01 mL/kg of 1:1000 solution SC q15-20min,
                 not to exceed 0.3 mL

            Nebulizer:
                   <2 years: 0.25 mL of 2.25% solution in 3 mL NS
                   >2 years: 0.5 mL of 2.25% solution in 3 mL NS



1.
Ipratropium
(Atrovent®)

     Anticholinergic bronchodilator acting at muscarinic
      receptors of parasympathetic nervous system.
      Inhibits smooth muscle contraction and is useful in
      patients with a significant bronchospasmodic
      component of the illness.
     Has antisecretory properties and, when applied
      locally, inhibits secretions from glands lining the
      nasal mucosa. It is synergistic with beta2-agonists.
     Dose Nebulizer: 250 mcg mixed with albuterol
      solution q20min for 3 doses, then q2-4h prn
Schuh S, Johnson D, Canny G, et al: Efficacy of adding nebulized ipratropium bromide to nebulized albuterol
therapy in acute bronchiolitis. Pediatrics 1992 Dec; 90(6): 920-3
Corticosteroids
Bronchiolitis
   Despite the prominent role that inflammation plays in the
    pathogenesis of airway obstruction, corticosteroid use remains
    controversial.
   In a recent randomized, double-blind, placebo controlled trial in
    children admitted to the hospital with RSV bronchiolitis, prednisolone
    (1 mg/kg/day orally for 7 days) was thought to be effective in
    accelerating the clinical recovery of these children (van Woensel).
   A study by Klassen and colleagues was conducted to determine the
    clinical benefit of oral dexamethasone in children admitted to
    hospital with bronchiolitis treated with nebulized salbutamol. The
    authors concluded that oral dexamethasone therapy does not affect
    the clinical course of children hospitalized with bronchiolitis.


    Currently, the evidence for the use of
    glucocorticosteroids for children with
    bronchiolitis is equivocal.
Corticosteroids
(Prednisone)

   Prednisone:
    – Block release of inflammatory mediators by inhibition of
      phospholipase and may be useful in patients with asthma
      or in bronchiolitis with asthmatic qualities.
   Dose:
    – 2 mg/kg PO initial, then 1 mg/kg/day in 1-2 daily doses;
      not to exceed 60 mg/d for 3-10 days
   Precautions
    – Hyperglycemia, edema, osteonecrosis, peptic ulcer
      disease, hypokalemia, osteoporosis, euphoria, psychosis,
      growth suppression, myopathy, and infections are possible
      complications of glucocorticoid use
So what do ya do?
Prevention
RSV Bronchiolitis

   RSV is the most common viral
    organism associated with severe
    bronchiolitis and prevention in
    high-risk patients is important!
   Palivuzimab (Synagis®)
     – Indicated for the prevention of
       serious lower respiratory tract
       (LRT) disease in pediatric patients
       at high risk of severe RSV disease,
       such as infants with
       bronchopulmonary dysplasia (BPD)
       or a history of premature birth
       (<35 weeks gestational age).
     – Has been available since 1999
Palivizumab
(Synagis®)
    Humanized monoclonal antibody
    Approved by the FDA for prevention of serious lower respiratory tract
     disease in pediatric patients at high risk of RSV infection. If the
     patient has already been infected with RSV this season and remains
     at high risk, consider palivizumab prophylaxis for the remainder of
     the season after resolution of the infection.
    Dose: 15 mg/kg/dose IM monthly during the RSV season
     (Nov - April)
    Dosage Form: Palivizumab is supplied in a 50 and 100 mg vial and
     should be reconstituted to a concentration of 100 mg/mL for
     intramuscular administration.
     (cost per 100 mg = $960)


IMpact--RSV Study Group: Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from
respiratory syncytial virus infection in high-risk infants. Pediatrics 1998 Sep; 102(3 Pt 1): 531-7
Palivizumab (Synagis®)
Children’s Hospital Guidelines
Should be given in patients meeting one of the following criteria:
1. Less than 24 months and current ventilator or oxygen dependence for any reason
2. Less than 24 months with chronic lung disease (BPD or other severe CLD) AND
         *on supplemental oxygen within the past 6 months or
         *on diuretic therapy as a replacement for oxygen therapy
3. Less than 24 months with severe chronic disorders compromising lung function (CDH, chest wall
     disorders, congenital lung malformation)
4. Gestational age 29-32 weeks and <6 months postnatal age at the start of RSV season or gestational age
     <28 weeks and <12 months postnatal age at the onset of RSV season.
5. Less than 12 months with high risk congenital heart disease and meets criteria as established by the
   Department of Cardiology

May be given in patients meeting one of the following criteria:
6. Gestational age 32-35 weeks if born < 6 months before the start of the RSV season and other risk factors
   present which include the following; Multiple Birth, Young Siblings, Day-Care Attendance, exposure to
   Tobacco
7. Less than 24 months at the onset of RSV season and severely immunocompromised (e.g. BMT,
   lung, heart, liver, or renal transplant) AND
       *is within a year of transplantation or
       *is on high doses of immunosuppressive agents
Complications and Prognosis
Bronchiolitis

   Complications:
     – Secondary infection, such as pneumonia
     – Respiratory failure.
     – Airway disease, such as asthma that may occur later in life.

   Prognosis:
     – The majority of children recover without sequelae. The course of disease
       is usually 7-10 days.

   Other:
     – Bronchiolitis has been identified as a risk factor for asthma, but this does
       not necessarily imply causation. The relationship between RSV infection
       and later development of asthma is still not understood, but children who
       have had bronchiolitis seem more likely to develop asthma than those
       who have not.
     – Children already predisposed to asthma may be more likely to wheeze
       when they have RSV or other respiratory infectious stimuli.
Morbidity and Mortality
Bronchiolitis

   Morbidity: Significant morbidity is rare.
    – Hospitalization:
           3% of cases
           17% of all infant hospitalizations
           3-7% Mechanical ventilation is required

   Mortality:
    – 1-2% of all hospitalized patients
    – 3-4% for patients with underlying cardiac or pulmonary
      disease.
    – Majority of deaths occur in infants younger than 6 months.
    – 4500 deaths per year